I-Corps: Delivery system for gene-based medicines

这个I-Corps项目更广泛的影响/商业潜力是开发一个模块化药物输送平台，用于输送基于基因的治疗药物。生物技术的下一个前沿是以基因为基础的药物，以治疗广泛的疾病，然而，它们的成功取决于提高其疗效和安全性的交付方法。目前用于输送这些药物的技术由于热稳定性或便携性、制造开发成本高和安全性而引起了对分销/运输的担忧。 该项目的成功转化可能会为非病毒基因递送提供新的范例，并通过降低成本，改善分布以及增强安全性和有效性为更广泛的人群提供更广泛的治疗方法。拟议的技术可以为基因治疗公司提供一个平台，在全球范围内提供他们的治疗方法，以推进个性化医疗。这个I-Corps项目的基础是利用改良的电穿孔技术开发基于DNA和mRNA的治疗药物递送平台。 电穿孔是一种用于基因递送的技术，其用电脉冲冲击细胞，允许治疗剂和其他分子渗透细胞壁。所提出的微针电穿孔平台能够实现基因和脉冲递送，显示出与研究使用电穿孔仪系统相当的性能。 所提出的技术提供涂层或注射治疗剂，以提高基因表达400倍，提高安全性。初步的体内研究显示，疗效与商业安全基准相当，包括COVID-19 DNA疫苗的测试。拟议的技术被设计为手持式，重量不到50克，在没有电力的情况下运行，以不到1美元的成本利用现有基础设施制造，并且可以由受过最低限度培训的人员操作或自我管理。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

The broader impact/commercial potential of this I-Corps project is the development of a modular drug-delivery platform for the delivery of gene-based therapeutic medicines. The next frontier in biotechnology is focused on gene-based medicines to treat a broad spectrum of diseases, however, their success is dependent on delivery methods to enhance their efficacy and safety. Current technologies used to deliver these medicines raise concerns regarding distribution/transportation due to thermostability or portability, high costs of development in manufacturing, and safety. The successful translation of this project may enable a new paradigm in non-viral gene delivery as well as broader access to these therapeutics for a wider population through lower costs, improved distribution, and enhanced safety and efficacy. The proposed technology may provide gene therapy companies with a platform to deliver their therapeutics on a global scale to advance 5personalized medicine. This I-Corps project is based on the development of a drug delivery platform for DNA and mRNA-based therapeutics utilizing a modified electroporation technology. Electroporation is a technique for gene delivery that shocks cells with an electric pulse, allowing therapeutics and other molecules to permeate cell walls. The proposed microneedle-electroporation platform enables both gene and pulse delivery showing comparable performance to research use electroporator systems. The proposed technology delivers coated or injected therapeutics to enhance gene expression 400-fold with improved safety. Preliminary studies in vivo have shown efficacy comparable to commercial benchmarks for safety, including tests with a COVID-19 DNA vaccine. The proposed technology is designed to be handheld and weighs less than 50g, operates without access to electricity, is manufactured with existing infrastructure at a cost of less than $1, and may be operated by minimally trained personnel or self-administered. Further development is required for the identification of specific biomedical applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.